OVERVIEW: What every clinician needs to know

Pathogen names and classification

Coryneform bacteria are a group of gram-positive, catalase-positive, non-spore-forming, non-motile, rod-shaped bacteria. The coryneform bacteria include the genera Corynebacterium, Arcanobacterium, Brevibacterium, Dermabacter, Microbacterium, Rothia, Turicella, Arthrobacter, and Oerskovia. They have also been called diphtheroids.

Lipophilic Corynebacteria

Corynebacterium jeikeium, C.urealyticum, C.afermentans subsp. lipophilum, C.accolens, C.macginleyi, C. tuberculostearicum, C.kroppenstedtii, C.bovis, C.lipophiloflavum, C.kutscheri, C.resistens, C. ureicelerivorans
Nonlipophilic, Fermentative Corynebacteria

C.ulcerans, C.pseudotuberculosis, C.xerosis, C.striatum, C.minutissimum, C. amycolatum, C. glucuronolyticum, C. argentoratense, C.matruchotii, C.riegelii, C.confusum
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Nonlipophilic, Nonfermentative Corynebacteria

C.afermentans subsp. afermentans, C.auris, C. pseudodiphtheriticum, C.propinquum
Arcanobacteria

Arcanobacterium haemolyticum, Arcanobacterium (Actinomyces) pyogenes, Arcanobacterium bernardiae
Miscellaneous Corynebacteria

Turicella otitidis

Arthrobacter Species

Brevibacterium casei

Dermabacter hominis

Rothia dentocariosa and Rothia mucilaginosa

Oerskovia species

Microbacterium species

Leifsonia aquatica

What is the best treatment?

Most of the coryneform bacteria are susceptible to vancomycin and teicoplanin, and also to daptomycin. In most instances, vancomycin is considered the treatment of choice with some exceptions:

C. ulcerans: use erythromycin, in addition to diphtheria antitoxin (DAT) for toxin producing cases
C. pseudotuberculosis: use a β-lactam antibiotic, macrolides, or tetracycline
Arcanobacterium haemolyticum: use erythromycin or azithromycin
Rothia species: use ampicillin.

Reported resistance patterns of some of the important pathogenic coryneforms include:

C. pseudodiphtheriticum: variable resistance to macrolides
C. jeikeium: resistant to penicillins, cephalosporins, and aminoglycosides, inducible resistance to macrolides
C. urealyticum: resistant to β-lactams, aminoglycosides, trimethoprim-sulfamethoxazole; variable susceptibility to fluoroquinolones, macrolides, and tetracycline
Arcanobacterium haemolyticum: resistance to trimethoprim-sulfamethoxazole
C. ulcerans: intermediate susceptibilities to vancomycin and pencillins

Reported mechanisms underlying resistance are as follows:

Resistance to macrolides, lincosamides and streptogramins B

rRNA methylase production causing methylation of the ribosome binding site

Active efflux of antibiotics from the cell (gene msrA; Gene mef)
Resistance to fluoroquinolones

Point mutations within the structural gene region of the gyrase subunit A
Resistance to tetracycline:

Active efflux of antibiotics from the cell (genes tetM; tetAB)
Resistance to beta lactamases

Presence of genes causing production of beta-lactamases or modification of penicillin-binding proteins
Resistance to glycopeptides (very rare)

Presence of the Van A gene

Alternative therapies include:

C. jeikeium: Quinupristin-dalfopristin, linezolid
C. urealyticum: teicoplanin, doxycycline, rifampin, linezolid
C. accolens: penicillin, erythromycin, ciprofloxacin, ceftriaxone, tetracycline
C. macginleyi: penicillin, gentamicin, ciprofloxacin, tetracycline, rifampin, linezolid
C. bovis: penicillin, amoxicillin, imipenem, ciprofloxacin, levofloxacin, clindamycin, gentamicin, rifampicin
C. ureicelerivorans: B-lactams, gentamicin, rifampin, tetracycline, linezolid
C. resistens: teicoplanin
C. auris: Tetracycline, rifampin, fluoroquinolones, gentamicin
C. pseudodiphtheriticum: penicillins, cephalosporins, doxycycline, glycopeptides
Arcanobacterium haemolyticum: Ciprofloxacin, clindamycin, doxycycline
Turicella otitidis: penicillins, cephalosporins, tetracyclines, fluoroquinolones, rifampin

How do patients contract this infection, and how do I prevent spread to other patients?

Epidemiology

Coryneform bacteria are widely distributed in the environment as normal inhabitants of soil and water. They are commensals colonizing the skin and mucous membranes of humans and other animals.

In the hospital setting, coryneforms may be cultured from the hospital environment, including surfaces and medical equipment. Coryneform bacteria other than C. diphtheriae have been isolated frequently in clinical specimens and are commonly considered contaminants without clinical significance. However, there is an increasing body of evidence of the pathogenicity of the coryneform bacteria, particularly as a cause of nosocomial infection in hospitalized and immunocompromised patients.

Several of the members of the genus Corynebacterium are better known as pathogens in animals and only incidentally cause infection in humans as zoonoses.

The incidence is probably increasing because of improved recognition of the pathogenic role of these organisms and better diagnostic capabilities.

Infection control issues

Standard precautions are recommended.

There is no vaccine.

Anti-infective prophylaxis is not recommended.

What host factors protect against this infection?

Higher risk for contracting infection with these organisms includes:

Immunosuppressed patients are at higher risk for infection with C.jeikeium.

Certain species have been reported to cause infection in those with a variety of devices: vascular catheters (C.jeikeium, C.macginleyi, C. afermentans subsp. lipophilum), intravascular devices (C.jeikeium, C.afermentans subsp. lipophilum), prosthetic valves (C.Jeikeium, C.afermentans subsp. lipophilum), CSF shunts (C.jeikeium), prosthetic joint infections (C.jeikeium, C.bovis), and urinary catheters (C.macginleyi).

What are the clinical manifestations of infection with these organisms?

The spectrum of human infections attributed to the coryneform bacteria can be divided into two general categories: community-acquired infections and nosocomial infections.

Community-acquired infections include pharyngitis, native valve endocarditis, genitourinary tract infections, acute and chronic prostatitis, and periodontal infections.

Nosocomial infections include intravascular catheter-associated bloodstream infections, native and prosthetic valve endocarditis, device-related infections, and postoperative surgical site infections. Common nosocomial pathogens include C. jeikeium, C. urealyticum, C. amycolatum, and C. striatum.
C.jeikeium: Septicemia from infected intravascular devices, native and prosthetic valve endocarditis
C.urealyticum: Chronic and recurrent urinary tract infection (UTI); encrusted cystitis ; encrusted pyelitis – also reported in peritonitis, endocarditis, pneumonia, septicemia, osteomyelitis, soft tissue infections, and superinfection of wounds
C.macginleyi: Conjunctivitis; rare reports of intravascular catheter–associated bloodstream infection, catheter-associated UTI
C.bovis: Endocarditis, chronic otitis media, central nervous system (CNS) infection, shoulder prosthetic joint infection, line-related septicemia
C.pseudodiphtheriticum: reported in endocarditis, respiratory infections particularly in immunocompromised hosts; also isolated from lymph nodes, eye, intervertebral disk
C. ulcerans: Has the potential to elaborate diphtheria toxin and cause an exudative pharyngitis in humans indistinguishable from diphtheria; skin infection; acute peritonitis in the setting of peritoneal dialysis.
Arcanobacterium haemolyticum: Pharyngitis (with associated exanthem in 50% of the cases); soft tissue infections, including chronic ulcers, wound infections, cellulitis, and paronychia; also reported to cause Lemierre’s disease, sepsis, sinusitis, orbital cellulitis, brain abscess, endocarditis, cavitary pneumonia, vertebral osteomyelitis, and periodontal abscesses

What common complications are associated with infection with these pathogens?

C.jeikeium: septicemia
C.urealyticum: chronic and recurrent UTI; encrusted cystitis ; encrusted pyelitis
C. ulcerans: death has been reported from toxin-induced cardiac injury; pneumonia; pulmonary nodules; necrotizing sinusitis
Arcanobacterium haemolyticum: sepsis

How should I identify the organisms?

Blood cultures and cultures from normally sterile sites have the highest yield of coryneforms that are true pathogens.
Routine Gram staining is the best staining technique. Typically, by gram stain, the morphology for coryneforms is pleomorphic, club shaped, gram-positive rods, which are non-motile and non-spore forming.
Standard blood agar plates are used to culture coryneforms from most specimens. Thioglycollate broth is used for wound cultures and standard automated blood culture systems. Special media used for species identification include tryptic soy agar with and without 1% Tween 80 to assess lipid-enhanced growth.
The expected appearance is that of pleomorphic, club shaped bacilli, demonstrating different forms at various stages of the life cycle, irregularly shaped, gram positive rods, non-motile, and non-spore forming.
Biochemical testing is used to identify the pathogens to the species level. Initial testing includes the catalase test with 3% H₂O₂. Additional tests include nitrate reduction, urea production, and hydrolysis patterns from glucose, maltose, sucrose, mannitol, and xylose.
A frequently used system of biochemical testing for medically relevant coryneform bacteria is the API CORYNE system, which includes 20 biochemical tests and will identify many of the important corynebacteria and other coryneform bacteria, including Arcanobacterium species and Brevibacterium species, as well as Rhodococcus equi, Listeria monocytogenes, Erysipelothrix rhusiopathiae, and Gardnerella vaginalis. An evaluation of the updated CORYNE database 2.0 gave correct identification for 90.5% of the coryneforms tested.
The RapID CB Plus system correctly identifies 80.9% of strains to the species level and an additional 12.2% to the genus level. It has the advantage of requiring only 4 hours to perform, compared with 24 hours for the CORYNE system.
Polymerase chain reaction (PCR) has been used by reference labs to speciate coryneforms. There is a PCR for C. ulcerans, which detects the presence of subunits A and B of the tox gene. It is not available commercially.
Other methods for identifying the organisms include:

n a few cases, the CAMP test helps to identify the organism to the species level.

A streak of a β-lysin-producing strain of Staphylococcus aureus is plated on sheep blood agar, and a streak of the test strain is plated perpendicular to it.

A positive CAMP reaction is noted if the CAMP factor, a cohemolysin secreted by the tested coryneform, enhances hemolysis in a synergistic fashion. Although most coryneform bacteria are CAMP negative, a few species, such as Corynebacterium auris and Corynebacterium gluronolyticum, have been shown to produce CAMP factor.

How do these organisms cause disease?

C. ulcerans has the potential to elaborate diphtheria toxin. Arcanobacterium haemolyticum produces toxins, including hemolysin and neuraminidase.
The diphtheria toxin produced by C.ulcerans can cause an exudative pharyngitis in humans indistinguishable from diphtheria.

WHAT’S THE EVIDENCE for specific management and treatment recommendations?

Funke, G, von Graevenitz, A, Clarridge III, J. “Clinical microbiology of coryneform bacteria”. Clin Microbiol Rev. vol. 10. 1997. pp. 125-59. (A nice review of the clinical microbiology of this group of organisms.)

Hollis, DG, Weaver, RE. “Gram-positive organisms: a guide to identification”. 1981. (A comprehensive review of the microbiology of all gram-positive organisms.)

Meyer, DK, Reboli, AC, Mandell, GL, Dolin, R, Bennett, JE. “Other Corynebacteria and Rhodococcus”. Principles and practice of infectious diseases. 2010. pp. 2695-706. (An excellent review of the taxonomy, microbiology, and clinical manifestations of all coryneform bacteria other than Corynebacterium diptheriae.)

Trost, E, Ott, L, Schneider, J. “The complete genome sequence of FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence”. BMC Genomics. vol. 11. 2010. pp. 728(Review of the genetics and virulence.)

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